Amyotrophic lateral sclerosis (ALS) is a fatal degenerative disease affecting motor neurons in the spinal cord, brainstem and cortex. We have previously shown that transplanting neuronal cells into the spinal cord delays the onset of motor symptoms in the G93A mouse model of ALS, but developing a potential treatment strategy around a committed neuronal cell or cell-line is not appropriate when there is widespread neurodegeneration as in ALS. Stem cells with their putative migratory abilities and multipotentiality may be able to protect dying motor neurons and prevent disease progression. However, the mechanism behind these effects is unknown. We hypothesize that stem cells from umbilical cord blood (hUCB) will have a neuroprotective effect through modulation of immune effectors. The purpose of this project is to determine whether the mononuclear hUCB (MNC hUCB) cell population can serve as a novel source of transplant cells to ameliorate behavioral deficits and extend lifespan in the G93A mouse model of ALS. In Aim 1 we will determine a dose response relationship between MNC hUCB transplantation in the ALS mouse and motor function and lifespan of the mouse. In Aim 2 we will determine the distribution and migration potential of the transplanted MNC hUCB cells to areas of degeneration and if they may adopt immune phenotypes in vivo. In Aim 3 we will determine the effect of the transplanted cells on host immune inflammatory response by examining cytokine expression in G93A mice. The results of this study may provide the basis for developing a novel, non-invasive therapy, easily accessed by ALS patients.